Biofilms are communities of bacteria that adhere to surfaces, and represent the physiological state in which most bacteria exist. Bacteria in biofilms behave differently than do bacterial cells suspended in culture medium (planktonic cells). Notably cells in biofilms are much more resistant to antibiotics and other biocides. Biofilms profoundly affect mankind. There are many links between biofilms and disease; it is estimated that more than half of all human bacterial infections involve biofilms. Biofilms growing on tissue, implants and medical tubing can be highly problematic and extremely difficult to treat. Staphylococcus aureus is major agent of nosocomial infections and capable of forming robust biofilms on biotic and abiotic surfaces. Yet, we know only a limited number of factors that contribute to S. aureus biofilm formation. Identified factors may become important vaccine and drug targets. Therefore, it will be important to elucidate the genetic factors involved in S. aureus biofilm formation. This proposal describes biochemical and genetic experiments designed to characterize novel factors that contribute to S. aureus biofilm formation.